U11IntrinsicallyunstructuredelementsExon1SRU2AF3'SSExon2U1Intron5'SSRepeatedrecognitionExon1Exon2GURAGUYNYURAYU2AF65U2AF35RSCRRM2SF1/BBPU2snRNAU2snRNPSF3b155p14Exon1Exon2GURAGURSCARRM3RRM2++++++YNYURYEcomplexAcomplexAlternativesplicingpatternsExonskipping(cassetteexon)Alternative5'SSAlternative3'SSMutuallyexclusiveexonsIntronretentionConstitutivesplicingConstitutiveexonAlternativeexonIntron5'3'Minor(U12type)spliceosomeSm/Sm20K25K31K35K48K59K65KSF3b155SF3b145SF3b130SF3b49SF3b14aSF3b14bSF3b10U11U12SmhPrp8hBrr2hSnu11440KhPrp6hLin1hDib1hPrp28U5Sm/LSmhSnu13hPrp31hPrp3hPrp4PPIHU6atacU4atacSm/LSmhPrp8hBrr2hSnu11440KhPrp6hDib1hPrp2827KhSad1hSnu66hSnu13hPrp31hPrp3hPrp4PPIHU5U6U4U6U4U5U6atacU4atacExon1Exon2GURAGUYNYURAYY10-12YAGUAUCCUUU5'SS3'SSBPSatacatacatacU6U4atacatacatacU11U12PolypyrimidinetractMajorMinorAGUCCUUAACUYACGAcomplex(pre-spliceosome)Bactcomplex(activatedspliceosome)AUACApre-mRNAmRNPIntron-lariatU11U11U11U11U12U12U12U5U6U4U5U6U4U5U5U5U4atacU6atacU6atacU6atacU6atacU6atacU4atac/U6atac•U5tri-snRNPU5Post-splicingcomplexBcomplex(pre-catalyticspliceosome)Ccomplex(catalyticstep1spliceosome)5'SSBPSStep1Step23'SSB*complex(catalyticallyactivatedspliceosome)U12U12U12AlternativeassemblypathwaysCross-intronAcomplexU1U1U2Cross-intronBcomplexOrU1U1U2GUGUCross-exonassembly......SRproteinsandhnRNPs35U2AF65U1...hnRNPU2...U1U1U1U2......35U2AF65RSRRMRRMPPPPPPPPPPOrOrSRPKsATPRRMRRMRSRSSRproteinPrp8(Jab1)Brr2IntermediateinhibitionFidelityandproofreadingINITIALASSEMBLYACTIVATIONPrp5(optimalsubstrate)Brr2,Snu114(Gprotein)Prp28(optimalsubstrate)CATALYSISDISASSEMBLYStep1Prp16(optimalsubstrate)Step2Prp22(optimalsubstrate)U15'SS3'SSBPDiscardby?Prp5(sub-optimalsubstrate)EcomplexU2U1Discardby?Prp28(sub-optimalsubstrate)AcomplexU2U6BcomplexPrp2(optimalsubstrate)Discardby?Prp2(sub-optimalsubstrate)SF3bBactcomplexSF3bB*complexDiscardbyPrp43Prp16(sub-optimalsubstrate)CcomplexDiscardbyPrp43Prp22(sub-optimalsubstrate)Post-splicingcomplexPrp43Intron-lariatcomplexLong-rangecontacts?SRU15'SSLong-...
